EP0858328B1 - Stable compositions containing n-propargyl-1-aminoindan - Google Patents

Stable compositions containing n-propargyl-1-aminoindan Download PDF

Info

Publication number
EP0858328B1
EP0858328B1 EP96930344A EP96930344A EP0858328B1 EP 0858328 B1 EP0858328 B1 EP 0858328B1 EP 96930344 A EP96930344 A EP 96930344A EP 96930344 A EP96930344 A EP 96930344A EP 0858328 B1 EP0858328 B1 EP 0858328B1
Authority
EP
European Patent Office
Prior art keywords
pharmaceutical composition
propargyl
aminoindan
weight
pharmaceutically acceptable
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP96930344A
Other languages
German (de)
French (fr)
Other versions
EP0858328A4 (en
EP0858328A2 (en
Inventor
Tirtsah Berger Peskin
Fanny Caciularu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Teva Pharmaceutical Industries Ltd
Original Assignee
Teva Pharmaceutical Industries Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=11068003&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP0858328(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Teva Pharmaceutical Industries Ltd filed Critical Teva Pharmaceutical Industries Ltd
Publication of EP0858328A2 publication Critical patent/EP0858328A2/en
Publication of EP0858328A4 publication Critical patent/EP0858328A4/en
Application granted granted Critical
Publication of EP0858328B1 publication Critical patent/EP0858328B1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention concerns formulations of R(+)-N-propargyl-1-aminoindan (referred to hereinafter as R(+) PAI) which is a selective irreversible inhibitor of the B-form of the enzyme monoamine oxidase used, for example, for the treatment of Parkinson's disease.
  • R(+) PAI a selective irreversible inhibitor of the B-form of the enzyme monoamine oxidase used, for example, for the treatment of Parkinson's disease.
  • MAO monoamine oxidase
  • MAO-B the B-form thereof as MAO-B.
  • GB 1 003 686 discloses a group of benzocycloalkane compounds in which the cycloalkane has from five to seven ring members and is substituted by an N-(alkynylalkyl)amino group, and their use as MAO inhibitors.
  • the patent further discloses the use of the subject compounds in admixture with a variety of substances including various alcohols such as a benzyl alcohol, stearyl alcohol, and methanol.
  • the patent does not teach how and by what criteria any of the many possible carriers and other ingredients are selected so as to overcome the stability problem of the product.
  • the object of the present invention is to provide stable formulations comprising an effective amount of R(+)-N-propargyl-1-aminoindan.
  • R(+) PAI the abbreviation of R(+) PAI.
  • a pharmaceutical composition comprising as an active ingredient a therapeutically effective amount of R(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable salt thereof, and at least one alcohol being a member selected from the group of pentahydric and hexahydric alcohols.
  • composition comprises at least 70% of said at least one alcohol.
  • the alcohol used in accordance with the invention is a member selected from the group of mannitol, xylitol and sorbitol.
  • the R(+) PAI-comprising composition may further include citric acid, preferably in an amount of 0.5 to 2% by weight.
  • compositions according to the invention may further comprise magnesium stearate, preferably in an amount of 0.1 to 0.5% by weight.
  • the composition further comprises citric acid in an amount specified above. Where the amount of said at least one alcohol is at least 70% by weight, the inclusion of citric acid is optional.
  • composition of the present invention may optionally also include conventional additives such as fillers, lubricants, disintegrants, glidants, flavoring agents, sweeteners, coloring agents, and the like, all as known per se.
  • conventional additives such as fillers, lubricants, disintegrants, glidants, flavoring agents, sweeteners, coloring agents, and the like, all as known per se.
  • fillers which may be used in accordance with the present invention are lactose, starch, microcrystalline cellulose, maltrin and the like.
  • compositions of the present invention may be prepared by methods known per se, familiar to those skilled in the art.
  • R(+) PAI and all other ingredients may be screened and mixed thoroughly in a suitable granulating machine. The granulation may occur in the presence of purified water, following which the composition is dried. The dry granulate may then be milled, lubricated and compressed into tablets.
  • R(+) PAI itself may be prepared, for example, according to the process described in Example 6B of WO95/11016.
  • the following procedure was adopted to determine the degradation of the formulations prepared.
  • the tablets were finely powdered and extracted with a diluent such as a mixture of water, acetonitrile and perchloric acid.
  • a diluent such as a mixture of water, acetonitrile and perchloric acid.
  • An aliquot of the extraction product was injected into an HPLC and eluted using the same mixture as said diluent mixture.
  • the area corresponding to the R(+) PAI compound was determined as was that of any other major peak.
  • the calculations of degradation percent was made by comparing the areas of the measured peaks with those obtained from the standard preparation.
  • Example 20 of WO95/11016 contained after storage 3.08% degradants whereas the formulations of Examples 2 and 3 contained 0.51% and less than 0.1% degradants, respectively.
  • Formulations according to the present invention and others according to the description given in Example 20 of WO95/11016 were prepared containing the ingredients shown in Table 1.
  • the formulations described in this Table are designated "PCT" when prepared in accordance with the disclosure in WO95/11016, or by a number which corresponds to the number of the Example in the present application, in which they are described.
  • the qualifying symbols of A, B, C or D appearing next to some of these designations denote certain variations in said formulations.
  • the percentage of degradation, presented in Table 2 was calculated for all the formulations of Table 1, after storing them for 1 month at 55°C or for 6 months at 40°C and 75% humidity. Those formulations stored according to the latter storing conditions are marked in the Table with an astrix (*).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Psychology (AREA)
  • Pain & Pain Management (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Solid Fuels And Fuel-Associated Substances (AREA)

Abstract

PCT No. PCT/IL96/00115 Sec. 371 Date Feb. 22, 1999 Sec. 102(e) Date Feb. 22, 1999 PCT Filed Sep. 18, 1996 PCT Pub. No. WO97/12583 PCT Pub. Date Apr. 10, 1997A pharmaceutical composition comprising as active ingredient a racemic, S(-), and R(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable salt thereof, and at least 60% by weight of at least one pentahydric or hexahydric alcohol. Optionally the composition may contain citric acid and magnesium stearate.

Description

  • The present invention concerns formulations of R(+)-N-propargyl-1-aminoindan (referred to hereinafter as R(+) PAI) which is a selective irreversible inhibitor of the B-form of the enzyme monoamine oxidase used, for example, for the treatment of Parkinson's disease. In the following the enzyme monoamine oxidase will be referred to as MAO and the B-form thereof as MAO-B.
  • GB 1 003 686 discloses a group of benzocycloalkane compounds in which the cycloalkane has from five to seven ring members and is substituted by an N-(alkynylalkyl)amino group, and their use as MAO inhibitors. The patent further discloses the use of the subject compounds in admixture with a variety of substances including various alcohols such as a benzyl alcohol, stearyl alcohol, and methanol. The patent, however, does not teach how and by what criteria any of the many possible carriers and other ingredients are selected so as to overcome the stability problem of the product.
  • The object of the present invention is to provide stable formulations comprising an effective amount of R(+)-N-propargyl-1-aminoindan. For the sake of simplicity, the abbreviation R(+) PAI, unless specified otherwise, will be used to denote the R(+) enantiomer of N-propargyl-1-aminoindan.
  • In accordance with the invention it was surprisingly found that the stability of formulations comprising R(+) PAI can be significantly improved by the incorporation of relatively large amounts of certain alcohols.
  • In accordance with the present invention there is provided a pharmaceutical composition comprising as an active ingredient a therapeutically effective amount of R(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable salt thereof, and at least one alcohol being a member selected from the group of pentahydric and hexahydric alcohols.
  • Preferably the composition comprises at least 70% of said at least one alcohol.
  • Typically the alcohol used in accordance with the invention, is a member selected from the group of mannitol, xylitol and sorbitol.
  • In accordance with the invention the R(+) PAI-comprising composition may further include citric acid, preferably in an amount of 0.5 to 2% by weight.
  • If desired, compositions according to the invention may further comprise magnesium stearate, preferably in an amount of 0.1 to 0.5% by weight. According to this embodiment, where the amount of said at least one alcohol is less than 70% by weight, the composition further comprises citric acid in an amount specified above. Where the amount of said at least one alcohol is at least 70% by weight, the inclusion of citric acid is optional.
  • The composition of the present invention may optionally also include conventional additives such as fillers, lubricants, disintegrants, glidants, flavoring agents, sweeteners, coloring agents, and the like, all as known per se. Examples of fillers which may be used in accordance with the present invention are lactose, starch, microcrystalline cellulose, maltrin and the like.
  • The compositions of the present invention may be prepared by methods known per se, familiar to those skilled in the art. For example, R(+) PAI and all other ingredients (with the exception of the lubricant, when used) may be screened and mixed thoroughly in a suitable granulating machine. The granulation may occur in the presence of purified water, following which the composition is dried. The dry granulate may then be milled, lubricated and compressed into tablets. R(+) PAI itself may be prepared, for example, according to the process described in Example 6B of WO95/11016.
  • The following non-limiting examples are given by way of illustration.
    • EXAMPLES EXAMPLE 1
  • mg/tablet
    R(+)-N-propargyl-1-aminoindan mesylate 3.12
    Mannitol 62.5
    Maltodextrin (Maltrin 150) 36.0
    Croscarmellose sodium (Ac-Di-Sol) 2.1
    Talc 1.5
    • EXAMPLE 2
  • mg/tablet
    R(+)-N-propargyl-1-aminoindan mesylate 1.56
    Mannitol 79.14
    Starch 10.0
    Pregelatinized starch 10.0
    Colloidal silicon dioxide 0.6
    Talc 2.0
    Stearic acid 2.0
    • EXAMPLE 3
  • mg/tablet
    R(+)-N-propargyl-1-aminoindan mesylate 3.12
    Mannitol 76.58
    Starch 10.0
    Pregelatinized starch 10.0
    Colloidal silicon dioxide 0.6
    Citric acid 1.0
    Talc 2.0
    • EXAMPLE 4
  • mg/tablet
    R(+)-N-propargyl-1-aminoindan mesylate 3.12
    Mannitol 69.88
    Lactose (hydrous) 14.0
    Starch 14.0
    Glyceryl Behenate (Compitrol 888 ATO) 2.0
    • EXAMPLE 5
  • mg/tablet
    R(+)-N-propargyl-1-aminoindan mesylate 3.12
    Mannitol 77.28
    Starch 10.0
    Starch STA-RX 1500 10.0
    Colloidal silicon dioxide, Aerosil 0.6
    Hydrogenated vegetable type I (Sterotex Dritex) 2.0
    • EXAMPLE 6
  • In order to compare the compositions of the present invention with those known in the prior art, two of the above formulations were compared with a formulation described in WO95/11016. Formulation of WO95/11016 (Example 20)
    mg/tablet
    R(+)-N-propargyl-1-aminoindan HCl 1.56
    Lactose (hydrous) 50.0
    Pregelatinized starch 36.0
    Microcrystalline cellulose 14.0
    Sodium starch glycolate 2.14
    Talc 1.0
    Magnesium stearate 0.5
  • This formulation, as well as those described under Examples 2 and 3 of the present application were subjected to 6 months at 40°C and 75% humidity. The percentage of degradants of the active material was assayed at the end of the six month period.
  • The following procedure was adopted to determine the degradation of the formulations prepared. The tablets were finely powdered and extracted with a diluent such as a mixture of water, acetonitrile and perchloric acid. An aliquot of the extraction product was injected into an HPLC and eluted using the same mixture as said diluent mixture. The area corresponding to the R(+) PAI compound was determined as was that of any other major peak. The calculations of degradation percent was made by comparing the areas of the measured peaks with those obtained from the standard preparation.
  • It was found that the formulation prepared according to the disclosure of Example 20 of WO95/11016 contained after storage 3.08% degradants whereas the formulations of Examples 2 and 3 contained 0.51% and less than 0.1% degradants, respectively.
    • EXAMPLE 7
  • Formulations according to the present invention and others according to the description given in Example 20 of WO95/11016 were prepared containing the ingredients shown in Table 1. The formulations described in this Table are designated "PCT" when prepared in accordance with the disclosure in WO95/11016, or by a number which corresponds to the number of the Example in the present application, in which they are described. The qualifying symbols of A, B, C or D appearing next to some of these designations denote certain variations in said formulations. The percentage of degradation, presented in Table 2, was calculated for all the formulations of Table 1, after storing them for 1 month at 55°C or for 6 months at 40°C and 75% humidity. Those formulations stored according to the latter storing conditions are marked in the Table with an astrix (*). As can be seen from Table 2, the stabilities of all the compositions of the present invention was superior to those of the prior art.
    Figure imgb0001
     Table 2
    Example No % Degradants Mannitol (%) Sorbitol (%) Xylitol (%) Magnesium stearate (%) Citric acid (%)
    PCT(*) 2.26 - 0.5 -
    PCT-A 2.76 - 0.49 -
    PCT-B 1.46 - 0.49
    PCT-C(*) 2.59 - 0.5 -
    1 1.22 59.4 - -
    1A 3.97 59.1 0.49 -
    1B 2.04 - 0.1 -
    1C 1.04 - 0.47 0.95
    1D 0.40 - 0.47 1.9
    2 0.29 75.1 - -
    2A 0.27 75
    3 0.02 72.7 - 0.95
    3A 0.02 74 0.95
    4 0.02 67.8 - -
    5 0.21 75 - -
    5A 0.32 75 0.1 -
    5B 0.65 76.2 0.47 -
    5C 0.52 74.7 0.47 -
    6 0.74 75.1 - -
    7 1.01 75.1 - -

Claims (26)

  1. A pharmaceutical composition comprising as an active ingredient a therapeutically effective amount of R(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable salt thereof, and at least one alcohol selected from the group consisting of pentahydric and hexahydric alcohols.
  2. The pharmaceutical composition of claim 1, wherein said at least one alcohol is mannitol, xylitol or sorbitol.
  3. The pharmaceutical composition of claim 1 or 2, wherein said at least one alcohol comprises at least 60% by weight of the pharmaceutical composition.
  4. The pharmaceutical composition of any one of claims 1 to 3 comprising as an active ingredient a therapeutically effective amount of R(+)-N-propargyl-1-aminoindan or a pharmaceutically acceptable salt thereof, and at least 70% by weight of mannitol.
  5. The pharmaceutical composition of any one of claims 1-4 which is in the form of a tablet.
  6. The pharmaceutical composition of claim 5, wherein the tablet comprises 77.28 mg of mannitol.
  7. The pharmaceutical composition of claim 5, wherein the tablet comprises 3.12 mg of the pharmaceutically acceptable salt of R(+) -N-propargyl-1-aminoindan.
  8. The pharmaceutical composition of claim 5, wherein the tablet comprises 1.56 mg of the pharmaceutically acceptable salt of R(+)-N-propargyl-1-aminoindan.
  9. The pharmaceutical composition of any one of claims 1-6, wherein said active ingredient is R(+)-N-propargyl-1-aminoindan.
  10. The pharmaceutical composition of any one of claims 1-6 wherein the active ingredient is a pharmaceutically acceptable salt of. R(+)-N-propargyl-1-aminoindan.
  11. The pharmaceutical composition of claim 10, wherein the pharmaceutically acceptable salt is the mesylate salt.
  12. The pharmaceutical composition of any one of claims 1-5 or 7-11, wherein the alcohol is mannitol.
  13. The pharmaceutical composition of any one of claims 1-12, further comprising citric acid.
  14. The pharmaceutical composition of claim 13, wherein the citric acid is present in an amount from 0.5 to 2% by weight of the pharmaceutical composition.
  15. The pharmaceutical composition of any one of claims 1-14, further comprising magnesium stearate.
  16. The pharmaceutical composition of claim 15, wherein the magnesium stearate is present in an amount from 0.1 to 0.5% by weight of the pharmaceutical composition.
  17. The pharmaceutical composition of claim 1 or 2, in which said at least one alcohol is present in an amount less than 70% by weight of the pharmaceutical composition, and further comprising citric acid in an amount from 0.5 to 2% by weight of the pharmaceutical composition.
  18. The pharmaceutical composition of claim 3 which is in the form of a tablet.
  19. The pharmaceutical composition of any one of claims 3 or 18, wherein said active ingredient is R(+)-N-propargyl-1-aminoindan.
  20. The pharmaceutical composition of any one of claims 3 or 18 wherein the active ingredient is a pharmaceutically acceptable salt of R(+)-N-propargyl-1-aminoindan.
  21. The pharmaceutical composition of claim 20, wherein the pharmaceutically acceptable salt is the mesylate salt.
  22. The pharmaceutical composition of any one of claims 3 or 18-21 wherein the alcohol is mannitol.
  23. The pharmaceutical composition of any one of claims 3 or 18-21, further comprising citric acid.
  24. The pharmaceutical composition of claim 23, wherein the citric acid is present in an amount from 0.5 to 2% by weight of the pharmaceutical composition.
  25. The pharmaceutical composition of any one of claims 3 or 18-24, further comprising magnesium stearate.
  26. The pharmaceutical composition of claim 25, wherein the magnesium stearate is present in an amount from 0.1 to 0.5% by weight of the pharmaceutical composition.
EP96930344A 1995-09-20 1996-09-18 Stable compositions containing n-propargyl-1-aminoindan Expired - Lifetime EP0858328B1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IL11535795 1995-09-20
IL11535795A IL115357A (en) 1995-09-20 1995-09-20 Stable compositions containing N-propargyl-1-aminoindan and polyhydric alcohols
PCT/IL1996/000115 WO1997012583A2 (en) 1995-09-20 1996-09-18 Stable compositions containing n-propargyl-1-aminoindan

Publications (3)

Publication Number Publication Date
EP0858328A2 EP0858328A2 (en) 1998-08-19
EP0858328A4 EP0858328A4 (en) 2001-07-11
EP0858328B1 true EP0858328B1 (en) 2007-05-23

Family

ID=11068003

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96930344A Expired - Lifetime EP0858328B1 (en) 1995-09-20 1996-09-18 Stable compositions containing n-propargyl-1-aminoindan

Country Status (13)

Country Link
US (1) US6126968A (en)
EP (1) EP0858328B1 (en)
JP (1) JP4108750B2 (en)
AT (1) ATE362755T1 (en)
AU (1) AU728524B2 (en)
CA (1) CA2232310C (en)
DE (1) DE69637096T2 (en)
DK (1) DK0858328T3 (en)
ES (1) ES2287940T3 (en)
HU (1) HU225859B1 (en)
IL (1) IL115357A (en)
PT (1) PT858328E (en)
WO (1) WO1997012583A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1729812A1 (en) 2004-02-27 2006-12-13 Niche Generics Limited Stable pharmaceutical composition comprising an ace inhibitor

Families Citing this family (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5744500A (en) 1990-01-03 1998-04-28 Teva Pharmaceutical Industries, Ltd. Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof
IL118836A (en) 1996-07-11 2001-01-11 Teva Pharma Pharmaceutical compositions comprising s-(-)-n-propargyl-1-aminoindan
JP2003512426A (en) 1999-10-27 2003-04-02 テバ ファーマシューティカル インダストリーズ リミティド Use of 1-aminoindan for the treatment of mania in bipolar mood disorder.
EP2526944B1 (en) 2002-11-15 2016-06-01 Teva Pharmaceutical Industries Limited Use of rasagiline with or without riluzole to treat amyotrophic lateral sclerosis
WO2006014973A2 (en) * 2004-07-26 2006-02-09 Teva Pharmaceutical Industries, Ltd. Pharmaceutical dosage forms including rasagiline
US8367105B2 (en) 2004-11-10 2013-02-05 Teva Pharmaceutical Industries, Ltd. Compressed solid dosage form manufacturing process well-suited for use with drugs of low aqueous solubility and compressed solid dosage forms made thereby
PT1729735E (en) * 2004-11-10 2007-08-06 Teva Pharma Compressed solid dosage form manufacturing process well-suited for use with drugs of low aqueous solubility and compressed solid dosage forms made thereby
AU2005309817B2 (en) * 2004-11-24 2011-08-18 Teva Pharmaceutical Industries, Ltd. Rasagiline orally disintegrating compositions
US20100167983A1 (en) * 2007-10-22 2010-07-01 Teva Pharmaceutical Industries, Ltd. Combination therapy with glatiramer acetate and rasagiline for the treatment of multiple sclerosis
ES2420404T3 (en) * 2005-02-17 2013-08-23 Teva Pharmaceutical Industries Ltd. Combination therapy with glatiramer acetate and rasagiline for the treatment of multiple sclerosis
JP5738509B2 (en) 2005-02-23 2015-06-24 テバ ファーマシューティカル インダストリーズ リミティド Rasagiline formulation with improved content uniformity
US7491847B2 (en) 2005-11-17 2009-02-17 Teva Pharmaceutical Industries, Ltd. Methods for isolating propargylated aminoindans
US7572834B1 (en) 2005-12-06 2009-08-11 Teva Pharmaceutical Industries, Ltd. Rasagiline formulations and processes for their preparation
AU2006326642B2 (en) 2005-12-09 2012-05-03 Technion Research And Development Foundation Ltd. Use of low-dose ladostigil for neuroprotection
EP1991214B1 (en) 2006-02-21 2015-08-05 Teva Pharmaceutical Industries, Ltd. Use of rasagiline for the treatment of multiple system atrophy
TW200744576A (en) 2006-02-24 2007-12-16 Teva Pharma Propargylated aminoindans, processes for preparation, and uses thereof
CN101442997B (en) 2006-04-03 2012-11-14 泰华制药工业有限公司 Use of rasagiline for the treatment of restless legs syndrome
DE202006020710U1 (en) 2006-05-09 2009-12-31 Teva Pharmaceutical Industries Ltd. Compositions with rosiglitazone maleate
EP1892233A1 (en) * 2006-08-18 2008-02-27 Ratiopharm GmbH New salts of the active component rasagiline
NZ577623A (en) 2006-12-14 2011-05-27 Teva Pharma Tannate salt of rasagiline
AU2007334428B2 (en) * 2006-12-14 2014-05-29 Teva Pharmaceutical Industries, Ltd. Crystalline solid rasagiline base
EP1987816A1 (en) * 2007-04-30 2008-11-05 Ratiopharm GmbH Adsorbate of a rasagiline salt with a water-soluble inactive ingredient
EP2194780A4 (en) * 2007-09-05 2010-10-27 Teva Pharma Method of treating glaucoma using rasagiline
US8188149B2 (en) * 2007-09-17 2012-05-29 Teva Pharmaceutical Industries, Ltd. Use of R(+)-N-propargy1-1-aminoindan to treat or prevent hearing loss
CN101909438A (en) * 2008-01-11 2010-12-08 泰华制药工业有限公司 Rasagiline formulations, their preparation and use
US20090247537A1 (en) * 2008-03-25 2009-10-01 William Dale Overfield Methods for preventing or treating bruxism using dopaminergic agents
EP2271612B1 (en) * 2008-03-31 2016-08-10 Actavis Group PTC EHF Rasagiline mesylate particles and process for the preparation thereof
MX2010013766A (en) * 2008-06-13 2011-03-15 Teva Pharmaceutical Ind Ltd Star Rasagiline for parkinson's disease modification.
AU2009260728B2 (en) 2008-06-19 2015-01-29 Teva Pharmaceutical Industries, Ltd. Process for preparing and drying solid rasagiline base
WO2009154782A1 (en) * 2008-06-19 2009-12-23 Teva Pharmaceutical Industries, Ltd. Process for purifying rasagiline base
US20100189788A1 (en) * 2009-01-23 2010-07-29 Teva Pharmaceutical Industries, Ltd. Delayed release rasagiline base formulation
EP2218444A3 (en) 2009-01-23 2010-08-25 Teva Pharmaceutical Industries, Ltd. Delayed release rasagiline formulation
CN102341104A (en) 2009-03-05 2012-02-01 桑多斯股份公司 Pharmaceutical composition containing 1h-inden-1-amine, 2,3-dihydro-n-2-propynyl-, (1r)-, methanesulfonate
EP2451771B1 (en) 2009-07-09 2014-06-18 Ratiopharm GmbH Salts of rasagiline and pharmaceutical preparations thereof
CN102048717B (en) † 2009-10-29 2014-02-19 重庆医药工业研究院有限责任公司 Stable rasagiline composition
US20110152381A1 (en) 2009-12-22 2011-06-23 Anton Frenkel 3-keto-n-propargyl-1-aminoindan
SG184547A1 (en) 2010-04-30 2012-11-29 Teikoku Pharma Usa Inc Propynylaminoindan transdermal compositions
EP2389927A1 (en) 2010-05-30 2011-11-30 Abdi Ibrahim Ilac Sanayi ve Ticaret Anonim Sirketi Pharmaceutical formulations of rasagiline
JP2013533287A (en) 2010-07-27 2013-08-22 テバ ファーマシューティカル インダストリーズ リミティド Use of rasagiline for the treatment of olfactory dysfunction
JP2013537530A (en) 2010-07-27 2013-10-03 テバ ファーマシューティカル インダストリーズ リミティド Rasagiline citrate dispersion
CN103476404B (en) 2011-03-24 2017-09-29 帝国制药美国公司 Transdermal composition comprising active agent layer and activating agent conversion coating
CN103857389A (en) * 2011-10-10 2014-06-11 泰华制药工业有限公司 Rasagiline citramide
EP2766004A4 (en) 2011-10-10 2015-04-22 Teva Pharma R(+)-n-methyl-propargyl-aminoindan
KR20140090996A (en) 2011-10-10 2014-07-18 테바 파마슈티컬 인더스트리즈 리미티드 R(+)-n-formyl-propargyl-aminoindan
US9913812B2 (en) 2011-11-09 2018-03-13 Teikoku Pharma Usa, Inc. Methods for the treatment of skin neoplasms
DE102012000786A1 (en) 2012-01-18 2013-07-18 Stada Arzneimittel Ag Process for the preparation of a solid pharmaceutical composition containing the active substance rasagiline
MX343986B (en) 2012-03-21 2016-12-01 Synthon Bv Stabilized pharmaceutical compositions comprising rasagiline salts.
WO2013175493A1 (en) 2012-04-09 2013-11-28 Cadila Healthcare Limited Stable oral pharmaceutical compositions
AR092168A1 (en) 2012-08-17 2015-03-25 Teva Pharma PARENTERAL FORMULATIONS OF RASAGILINA
JP6050896B2 (en) 2012-11-02 2016-12-21 テイコク ファーマ ユーエスエー インコーポレーテッド Propinylaminoindan transdermal composition
ES2524865T1 (en) * 2013-02-06 2014-12-15 Galenicum Health S.L. Stable pharmaceutical compositions in the form of immediate-release tablets
ES2502140T1 (en) * 2013-02-06 2014-10-02 Galenicum Health S.L. Rasagiline hemitartrate immediate-release tablets
CN115400090A (en) * 2022-10-09 2022-11-29 北京新领先医药科技发展有限公司 Orally disintegrating tablet composition of rasagiline and preparation method thereof

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1187017A (en) * 1966-07-16 1970-04-08 Aspro Nicholas Ltd Substituted 1-Amino Indanes and Tetrahydronaphthalens
GB8909793D0 (en) * 1989-04-28 1989-06-14 Beecham Group Plc Pharmaceutical formulation
IL92952A (en) * 1990-01-03 1994-06-24 Teva Pharma R-enantiomers of n-propargyl-1-aminoindan compounds, their preparation and pharmaceutical compositions containing them
CA2039742A1 (en) * 1990-04-23 1991-10-24 Andrew B. Dennis Tablet composition and method for problem pharmaceutical materials
IL99759A (en) * 1991-10-16 1997-06-10 Teva Pharma Mono-fluorinated derivatives of n-propargyl-1-aminoindan, their preparation and pharmaceutical compositions containing them
IL111240A (en) * 1993-10-18 2001-10-31 Teva Pharma Salts of r(+) - enantiomers of n- propargyl-1-aminoindan and pharmaceutical compositions comprising them
IL112779A (en) * 1994-03-01 1999-11-30 Gergely Gerhard Granular product or tablet containing an efferescent system and an active pharmaceutical substance and its preparation
JP3273141B2 (en) * 1995-03-02 2002-04-08 アール． ピー． シェーラー リミテッド Pharmaceutical composition comprising monoamine oxidase B inhibitor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1729812A1 (en) 2004-02-27 2006-12-13 Niche Generics Limited Stable pharmaceutical composition comprising an ace inhibitor

Also Published As

Publication number Publication date
HUP9802999A3 (en) 1999-05-28
IL115357A0 (en) 1995-12-31
HU225859B1 (en) 2007-11-28
AU728524B2 (en) 2001-01-11
US6126968A (en) 2000-10-03
AU6942796A (en) 1997-04-28
DK0858328T3 (en) 2007-09-03
CA2232310C (en) 2008-01-08
JPH11512736A (en) 1999-11-02
WO1997012583A2 (en) 1997-04-10
DE69637096T2 (en) 2008-01-31
PT858328E (en) 2007-08-20
ES2287940T3 (en) 2007-12-16
HUP9802999A2 (en) 1999-04-28
EP0858328A4 (en) 2001-07-11
JP4108750B2 (en) 2008-06-25
ATE362755T1 (en) 2007-06-15
CA2232310A1 (en) 1997-04-10
IL115357A (en) 2000-01-31
WO1997012583A3 (en) 1997-06-05
DE69637096D1 (en) 2007-07-05
EP0858328A2 (en) 1998-08-19

Similar Documents

Publication Publication Date Title
EP0858328B1 (en) Stable compositions containing n-propargyl-1-aminoindan
US6384020B1 (en) Rapid immediate release oral dosage form
EP0711154B1 (en) Stabilized pharmaceutical composition containing bupropion
US6767558B2 (en) Inhibiting oxidative degradation of pharmaceutical formulations
US8741342B2 (en) Pharmaceutical compositions comprising entacapone, levodopa, and carbidopa
NZ502228A (en) Multiparticulate tablet with fast rate of disintegration
CA2137164C (en) A new composition containing selegiline
EP0800384B1 (en) Pharmaceutical tablet formulations for direct compression
AU771490B2 (en) Stable compositions containing N-propargyl-1-aminoidan
WO2013106526A1 (en) Saxagliptin parmaceutical formulations
EP1416918B1 (en) Synergistic filler composition
BG61242B2 (en) Solid pharmaceutical composition for oral administration based on dapiprazole
US8263124B2 (en) Anthistamine-decongestant pharmaceutical compositions
US5817336A (en) Composition containing selegiline
EP1518551B1 (en) Solid dosage form comprising caffeine
AU663995C (en) A new composition containing selegiline
KR20220140343A (en) Oral composite formulation comprising evogliptin and metformin and method for preparing the same
KR100561025B1 (en) Stable ramipril tablets to be manufactured by direct compression

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19980420

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: LT PAYMENT 980420;LV PAYMENT 980420

A4 Supplementary search report drawn up and despatched

Effective date: 20010529

AK Designated contracting states

Kind code of ref document: A4

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

17Q First examination report despatched

Effective date: 20030319

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Extension state: LT LV

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REF Corresponds to:

Ref document number: 69637096

Country of ref document: DE

Date of ref document: 20070705

Kind code of ref document: P

REG Reference to a national code

Ref country code: PT

Ref legal event code: SC4A

Free format text: AVAILABILITY OF NATIONAL TRANSLATION

Effective date: 20070806

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

REG Reference to a national code

Ref country code: GR

Ref legal event code: EP

Ref document number: 20070402332

Country of ref document: GR

REG Reference to a national code

Ref country code: SE

Ref legal event code: TRGR

REG Reference to a national code

Ref country code: CH

Ref legal event code: NV

Representative=s name: E. BLUM & CO. AG PATENT- UND MARKENANWAELTE VSP

ET Fr: translation filed
REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2287940

Country of ref document: ES

Kind code of ref document: T3

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20080226

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: MC

Payment date: 20150914

Year of fee payment: 20

Ref country code: DE

Payment date: 20150922

Year of fee payment: 20

Ref country code: CH

Payment date: 20150918

Year of fee payment: 20

Ref country code: IE

Payment date: 20150917

Year of fee payment: 20

Ref country code: FI

Payment date: 20150911

Year of fee payment: 20

Ref country code: ES

Payment date: 20150928

Year of fee payment: 20

Ref country code: PT

Payment date: 20150915

Year of fee payment: 20

Ref country code: GB

Payment date: 20150917

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GR

Payment date: 20150915

Year of fee payment: 20

Ref country code: FR

Payment date: 20150922

Year of fee payment: 20

Ref country code: BE

Payment date: 20150918

Year of fee payment: 20

Ref country code: LU

Payment date: 20151008

Year of fee payment: 20

Ref country code: AT

Payment date: 20150921

Year of fee payment: 20

Ref country code: SE

Payment date: 20150923

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IT

Payment date: 20150924

Year of fee payment: 20

Ref country code: DK

Payment date: 20150918

Year of fee payment: 20

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20150917

Year of fee payment: 20

REG Reference to a national code

Ref country code: DE

Ref legal event code: R071

Ref document number: 69637096

Country of ref document: DE

REG Reference to a national code

Ref country code: DK

Ref legal event code: EUP

Effective date: 20160918

REG Reference to a national code

Ref country code: NL

Ref legal event code: MK

Effective date: 20160917

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: GB

Ref legal event code: PE20

Expiry date: 20160917

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20160917

REG Reference to a national code

Ref country code: SE

Ref legal event code: EUG

REG Reference to a national code

Ref country code: IE

Ref legal event code: MK9A

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK07

Ref document number: 362755

Country of ref document: AT

Kind code of ref document: T

Effective date: 20160918

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20160927

REG Reference to a national code

Ref country code: ES

Ref legal event code: FD2A

Effective date: 20161227

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20160918

REG Reference to a national code

Ref country code: GR

Ref legal event code: MA

Ref document number: 20070402332

Country of ref document: GR

Effective date: 20160919

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION

Effective date: 20160919